P147 M2 macrophage associated fibrosis in early stage systemic sclerosis: an update on plasma biomarkers

Abstract Background/Aims Systemic sclerosis is an autoimmune connective tissue disease characterised by vasculopathy and fibrosis. The CCN family of matricellular proteins have a regulatory role in inflammation and fibrosis. CD206, an M2 macrophage surface marker, is cleaved by metalloproteases to release soluble form of CD206; this acts as an active disease marker in systemic sclerosis. We investigated the profile of CCN2 and CCN3 in the presence of soluble CD206 (sCD206) in patients with early and late stage diffuse systemic sclerosis (dcSSc). Methods Patients with a diagnosis of dcSSc at the UCL Centre for Rheumatology and Connective Tissue Diseases were recruited. Informed consent was obtained from patients and healthy controls (HC). Blood samples were taken from which plasma was isolated and stored at -80 °C prior to assay. Expression of CCN2, CCN3, and sCD206 was measured in these plasma samples by ELISA. Study participants were categorised into healthy controls (n = 20), early stage dcSSc (n = 20) and late dcSSc (n = 20), with early stage defined as the blood sample taken within two years since diagnosis, and late stage defined as over five years since diagnosis. Results Plasma CCN2, CCN3 and sCD206 levels were significantly higher in early dcSSc patients, when compared to HC. CCN2 was raised in early dcSSc patients (early dcSSc mean 20,221pg/ml, SD 16,503, p < 0.05) with concentration in late disease matching that of HC (late dcSSc 12,893pg/ml, HC 11,289pg/ml). CCN3 was significantly higher in early and late disease when compared to HC (early mean 16,526pg/ml, late 12,838pg/ml, HC 4,201pg/ml, p < 0.05). sCD206 levels were higher in early dcSSc (mean 5356pg/ml, SD 3154, p < 0.05), with there being no significance between levels in late dcSSc (mean 4184pg/ml, SD 3900, p > 0.05) and HC (mean 3319pg/ml, SD 1925). CCN2 expression was higher compared to that of CCN3 in early disease, with CCN2:CCN3 ratio elevated in early dcSSc (mean 3.17, SD 8.26) compared to late dcSSc (mean 1.26, SD 0.99) and HC. Conclusion This investigation demonstrates that upregulation of CCN2 and CCN3 expression has a regulatory role in fibrosis in early stage dcSSc. These biomarkers of M2 macrophage associated fibrosis are to be correlated with their clinical phenotype and have potential for a role in targeted treatment of systemic sclerosis. Disclosure L.A. Leeves: None. Z. Kannan: None. Y. Ali: None. L. Pan: None. T. Malley: None. D. Abraham: None. A. Leask: None. B. Riser: None. B. Ahmed Abdi: None. R.J. Stratton: None.